This application proposes a Phase 1 clinical trial of thymus transplantation involving 8 subjects with complete DiGeorge anomaly. The objective of this study is to determine if thymus tissue cultured in a serum free medium is comparable in its ability to support thymopoiesis and thymus (T) cell reconstitution as thymus tissue cultured in media containing fetal bovine serum. The use of serum free medium would reduce the concerns of exposure of animal products including the potential for exposure to bovine spongiform encephalopathy (BSE). Though in vitro studies of cultured thymus tissue indicate serum free and serum containing media are comparable, there are no in vitro or animal studies that recapitulate the thymus engraftment and T cell reconstitution in athymic infants. The composition of the medium for thymus tissue culture must be finalized prior to initiation of a pivotal trial for thymus transplantation. Results of the pivotal trial will be submitted for a Biologic License Application. Though the lack of na[unreadable]ve T cells results in a fatal immunodeficiency, 73% of 49 infants treated with thymus transplantation survive and all over 2 years after transplantation have good T cell reconstitution. Eight infants with complete DiGeorge anomaly (<50/mm3 na[unreadable]ve T cells) will be transplanted with thymus tissue cultured in serum free medium. Four subjects will have "typical" complete DiGeorge anomaly (no rash) and four with have "atypical" complete DiGeorge anomaly with rash and circulating oligoclonal T cells. The initial two typical and two atypical subjects will receive thymus cultured in serum containing medium and also, in a separate site, thymus cultured in serum free medium. The remaining subjects will receive only thymus cultured in serum free medium. The primary clinical safety outcomes will be survival at 1 year after transplantation and absence of graft versus host disease within the first year after transplantation. The secondary safety outcome measure is the incidence of autoimmune disease at 2 years after transplantation. Other secondary outcomes are the number of na[unreadable]ve cluster of differentiation (CD4) T cells at one year, the number of CD4 T cells at one year, the T cell proliferative response to the mitogen phytohemagglutinin (PHA) at one year, and the diversity of the CD4 T cell receptor beta variable chain (TCRBV) at one year. Criteria based on the primary and secondary outcomes are included in the protocol which will allow for acceptance or rejection of the serum free medium for use in the pivotal trial. Lastly in a descriptive analysis using immunohistochemistry and real time polymerase chain reaction (PCR), the allograft biopsies obtained at 2 months after transplantation of tissue cultured in serum free medium will be compared with biopsies in which serum was used in the culture medium. The focus of these experiments is the development of thymopoiesis and normal presentation of promiscuously expressed antigens in the thymus.